Wellcome Trust Centre for Gene Regulation and Expression

Wellcome Trust Centre for Gene Regulation and Expression

The machinery of life is incredibly complex, says Julian Blow, deputy director of the Wellcome Trust Centre for Gene Regulation and Expression at Dundee University.

"If you think of a cell as a car engine, we have a parts list now, in terms of big things, like pistons and crankshafts. But there are all sorts of processes going on in a cell that we still don't know much about.

"Let me give you an overview of what we're doing here to learn more about them.

"Genetic information is stored in DNA inside the nucleus of a cell. That gets turned into instructions that produce proteins that do the work of the cell. That's the gene expression part. Some of our research groups are working on that."

Other groups study how a cell controls which genes are switched on or off, and how the DNA is maintained and copied, he says. "We look at how DNA is read, turned into RNA and then into protein - and how all that is regulated."

Pure and applied

What happens inside a living cell is the essence of biology, says Professor Blow. "Pretty much every living thing has DNA - and it all needs to be properly maintained and propagated. The instructions encoded in the DNA need to be turned into proteins that do the work of the cell.

"How cells work is the basis of what life is."

This is what the researchers at the Wellcome Trust Centre for Gene Regulation and Expression aim to understand, he says. "It is mostly basic research. But many of these processes go wrong in different diseases.

"Cancer for instance has strong links with gene regulation. So the work of many of our groups has implications for understanding what goes wrong in cancer cells.

"We don't develop drugs all the way ourselves. But we do talk to drug development people about our findings. And we work with them.

Most of the fundamental principles about how cells work have now been discovered, Professor Blow believes. "Although I could be wrong about that.

"We have an inventory now of all the proteins inside a cell. So you can tell simple stories about them and what they are doing. But that only gets you so far. There is an awful lot going on in a cell that we don't yet understand."

Moving parts

Biologists now have a complete parts list for the inside of a living cell, says Professor Blow, deputy director of the Wellcome Trust Centre for Gene Regulation and Expression. "We can look at all the proteins in a cell or in one of its organelles.

"You can then study a process and find a protein that drives it. So you can map out simple pathways - A goes to B goes to C."

That's how cell biology has traditionally been done, he says. But scientists are now beginning to look at - and understand - the effects of all the other proteins around.

"We knew about major proteins doing big things. But we're now finding that every one of these has lots of other proteins guiding what's going on, regulating it, allowing it to talk to other processes in the cell.

"The complete parts list means we can start moving away from the simple stories, the linear paths, and start looking at complicated networks of interactions with feedback loops.

"It's called proteomics. It means biology is becoming much more quantitative and numerical.

Realising that, the Centre has taken on two physicists to help with handling and interpreting the data, he says. "They have experience with the amount of data we're now getting in biology"

Techniques

Modern microscopes are one source of the vast amount of data that biologists produce and need to handle these days, says Professor Blow. "It's no longer a matter of just looking at an image in a microscope and trying to interpret it.

"Suppose you're interested in one of the many thousands of proteins in a cell. You can label it so that it will fluoresce under a certain wavelength of light. Then you can follow it going about its business in a living cell.”

The other vital piece of kit for doing modern cell biology is a mass spectrometer, says Professor Blow. "We use this to separate out and identify proteins and bits of protein with incredible accuracy.”

Both living cell microscopy and mass spectrometry generate huge quantities of data that need to be analysed, says Professor Blow. "They are high-throughput - and in complementary ways.

"Mass spectrometry might show for instance that a protein has changed its behaviour in a population of cells. So you can then tag it fluorescently and study what it's doing in a single cell using a microscope."

Both these methods are quite common in modern cell biology, says Professor Blow. "But our use of these complementary technologies is a real driving force here at the Centre

"We're using cutting-edge technology to ask cutting-edge biological questions. It's one reason we are particularly effective

Culture

The other feature that makes for good science at the Wellcome Trust Centre for Gene Regulation and Expression is the culture there, says Julian Blow.

"We have these open-plan labs which is quite unusual. People aren't shut away from each other. They're encouraged to talk, interact, share technology and ideas.

"We have all sorts of activities to make us feel part of a community - and to make science fun. Come in any weekend and there'll be people here. It's a fertile place for exchanging ideas."

That doesn't mean only among the scientific community, he says. "We're keen on public engagement. We want to get our science out there.

"Whether they come into science to understand how the world works or to cure disease or for some other reason, good scientists become very enthusiastic about what they do. They want to communicate it to people."

"There is a lot more to discover and, as I said at the start, the inside of a living cell is very complicated indeed. But molecular biology has made enormous progress in the 50 years or so it has existed.

"There is a vast, unexplored territory still out there. But to a scientist that is not daunting. It's exciting."